Project Summary Post-traumatic stress disorder (PTSD), a debilitating psychological disorder characterized by aberrant responses to threat stimuli, is a major public health concern associated with significant morbidity and mortality, especially within the veteran population. The only effective therapies for PTSD (i.e., exposure therapies) create new safety responses that compete with and mask?but do not alter?the problematic threat responses. Additionally, there is no conclusive evidence supporting psychopharmacological interventions to treat PTSD, which further highlights a lack of knowledge of the neurobiology of the disorder. For example, despite the prevalence of trauma exposure in both the general and veteran populations, the specific susceptibilities or alterations that determine risk and resilience for ensuing psychopathology are unknown. Laboratory models are frequently used to study threat memory processing in PTSD?however, these models erase the nuance of the vivid, multiplex stimuli that typically trigger aberrant responding in PTSD. Thus, our understanding of PTSD may be limited by the gap between laboratory models of threat and naturalistic threat stimuli. An understanding of the precise neurobiological impairment underlying aberrant responses to naturalistic threat stimuli in PTSD will support therapies that go beyond masking symptoms, target the root issue, and pave the way for curative interventions. The present proposal aims to define the dysregulated neural circuits that relate to PTSD symptom severity in a population of American veterans who served in Iraq or Afghanistan. We will utilize newly developed multivariate functional magnetic resonance imaging (fMRI) techniques (i.e., multivariate pattern analyses; MVPA) to identify dynamic patterns of brain activity during naturalistic threat exposure. By monitoring neural representations of dynamic, naturalistic stimuli, we will determine whether the brain differentially processes naturalistic threat stimuli in PTSD. This is a step toward identifying the root cause of aberrant threat responses, as aberrant neural representations of threatening stimuli may necessarily lead to disordered physiological responses to those dysregulated representations. Since abnormal threat responses in PTSD are triggered both by threatening cues in the external environment as well as internally re-living past negative memories, the present proposal will evaluate and quantify two scenarios. It will evaluate the neural processing of aversive, naturalistic stimuli by quantifying the stability of neural representations elicited by a combat movie. The proposal will also evaluate the neural processing of personal trauma memories by quantifying the stability of neural representations during repeated reactivations of autobiographical memories. This project will enhance our understanding of whether and how threat stimuli are differentially represented in PTSD and facilitate development of treatment options that go beyond masking the symptoms of PTSD and target the underlying cognitive impairment.